CX3CR1 polymorphisms associated with an increased risk of developmental dysplasia of the hip in human

Developmental dysplasia of the hip, also termed congenital hip dislocation, is one of the major causes of children disability and early onset osteoarthritis. Previous study has identified a variant of CX3CR1 underlying this disorder in a large family. However, genetic evidence from population was still lacking. Here, we performed a case‐control association study by genotyping two SNPs of CX3CR1, rs3732378, and rs3732379, in 689 unrelated hip dislocation patients and 689 normal controls. Genotyping results showed significant difference in genotype distributions of both two polymorphisms (p = 0.003 for rs3732378 and p = 0.017 for rs3732379). The minor allele frequency of rs3732378 was higher in cases (4.79%) than in controls (2.47%), predisposing carriers to hip dislocation with a 2.25‐fold risk (OR = 2.25, 95%CI 1.42–3.56) after adjustment for gender. Another SNP, rs3732379, was also significantly associated with an increased risk of hip dislocation (adjusted OR = 1.84, 95%CI 1.19–2.84). Through the population study, we demonstrated that CX3CR1 was candidate for the pathogenesis of the disorder, and identified rs3732378 and rs3732379 as susceptibility loci instead of disease‐causing mutations. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:377–380, 2017.

[1]  W. Tian,et al.  Two single-nucleotide polymorphisms in the DKK1 gene are associated with developmental dysplasia of the hip in the Chinese Han female population. , 2014, Genetic testing and molecular biomarkers.

[2]  D. Szukiewicz,et al.  The Chemokine CX3CL1 (Fractalkine) and its Receptor CX3CR1: Occurrence and Potential Role in Osteoarthritis , 2014, Archivum Immunologiae et Therapiae Experimentalis.

[3]  Mark A. Levenstien,et al.  Developmental Dysplasia of the Hip: Linkage Mapping and Whole Exome Sequencing Identify a Shared Variant in CX3CR1 in All Affected Members of a Large Multigeneration Family , 2013, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[4]  Binbin Wang,et al.  Two single nucleotide polymorphisms in the GDF5 gene are associated with development dysplasia of the hip in Chinese female population , 2013, Science China Life Sciences.

[5]  W. Tian,et al.  Association analysis between HOXD9 genes and the development of developmental dysplasia of the hip in Chinese female Han population , 2012, BMC Musculoskeletal Disorders.

[6]  D. Viskochil,et al.  Familial Predisposition to Developmental Dysplasia of the Hip , 2009, Journal of pediatric orthopedics.

[7]  S. Rishpon,et al.  Developmental dysplasia of the hip: Risk markers, clinical screening and outcome , 2008, Pediatrics international : official journal of the Japan Pediatric Society.

[8]  E. Calzolari,et al.  Exclusion of COL2A1 and VDR as Developmental Dysplasia of the Hip Genes , 2008, Clinical orthopaedics and related research.

[9]  F. Canovas,et al.  Microenvironmental changes during differentiation of mesenchymal stem cells towards chondrocytes , 2007, Arthritis research & therapy.

[10]  S. Jacobsen,et al.  Hip dysplasia: a significant risk factor for the development of hip osteoarthritis. A cross-sectional survey. , 2005, Rheumatology.

[11]  K. Søballe,et al.  Hip dysplasia and osteoarthrosis , 2005, Acta orthopaedica.

[12]  H. Patel.  Preventive health care, 2001 update: screening and management of developmental dysplasia of the hip in newborns. , 2001, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[13]  K Shoppee,et al.  Developmental Dysplasia of the Hip , 1992, Orthopedic nursing.

[14]  P. Harper,et al.  Report of the delegation of clinical geneticists to China, Spring 1986. , 1987, Biology and society : the journal of the Eugenics Society.